Taken together with the above results, this suggests that the activation of primary T cells requires at least two signals and that IL-2produced by naive T cells in vivo may act in an autocrine fashion to allow them to proliferate and differentiate.

PGE2 primes naive T cells in a dose-dependent fashion for production of high levels of IL-4, IL-10 and IL-13, and very low levels of IL-2, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and TNF-beta.

These cells appear to be in a state of marginal activation in that they also express low levels of the interleukin 2 receptor (Tac antigen) and have increased cell size as compared to the naive T cells.

We demonstrate in this report that antibodies to the B7.2 molecule inhibit IL-2production in vivo caused by anti-CD3 administration, suggesting that anti-CD3 monoclonal antibodies (mAb) stimulate naive T cells in vivo in a co-stimulation-dependent fashion.

Differences were observed in the cytokine responses to H1, H3, and H5, whereas both IL-2 and IFN-gamma production characteristic of memory responses were observed for H1 and H3, and H5-specific responses elicited primarily IL-2 and little or no IFN-gamma, consistent with a naive T cell phenotype.

Dendritic cells (DCs) and DC-derived cytokines allowed naive T cells to proliferate selectively in response to IL-4, and potently boosted the response of T(CM) to IL-7 and IL-15 by increasing the expression of the IL-2/IL-15Rbeta and the common gamma chain (gamma(c)).

A further analysis of IL-2 and IL-2R expression indicated: 1) The first synthesis of IL-2 was detected at the same ligand concentration in both primed and naive T cells, but primed T cells made much more IL-2 as the ligand concentrations increased; 2) primed T cells expressed about fivefold more IL-2 receptor (R) than naive T cells, despite the fact that the antigen dose-response curves with respect to the percentage of cells expressing IL-2R were identical.

Thus, naive T cells are sensitive to CD28-mediated co-stimulation during superantigen-mediated responses but IL-2production can be induced by high doses of superantigens in the presence of APC expressing weak co-stimulatory activity.

After a cycle of HAART + IL-2, followed by therapy interruption, CD45RA and CD62L are detected on virions rarely, indicating that even during virus rebound, expanded naive T cells do not become a major target of virus replication.

These data indicate that CD9-mediated costimulation of TCR-triggered naive T cells leads to activation followed by apoptosis as the result of failure to generate a positive signal for sufficient levels of IL-2production.

In addition, this age-related decrease in induction of nuclear NFkappaB correlated with decrease in intracellular IL-2 receptor expression and anti-CD3-induced proliferation of both memory and naive T cells subsets.